At present, the insulin used in the clinical treatment of diabetes is in the form of an injectable formulation, and in most cases is self-administered by a comparatively simple subcutaneous injection. The characteristics of this type of drug are such that the patient must self-administer before meals, once to four times a day for life. This troublesome procedure is only one of the many problems associated with the treatment of diabetes.
Preparations for nasal administration have been proposed as a remedy to the difficulties associated with subcutaneous administration. For example, an insulin formulation in which 90 w/w % of the particle diameters ranged from 20-150 μm, using crystalline cellulose as a basic material was described in JP-6242888-B. Under the suggestion that ‘Physiological polypeptides for nasal mucosal absorption are preferably water-soluble’ in this preparation, the practical example described in the said publication show a formulation in which 90 w/w % or more of the particle diameters ranged from 75-149 μm can be obtained after dissolving insulin in 0.1N HCl, freeze-drying, mining the soluble insulin thus obtained with crystalline cellulose, and sifting.
In comparison with the above-mentioned JP-6242888-B, JP-1059841-A (corresponding to EP-943326-A1) with regard to high hydrophilic drugs, high lipophilic drugs and peptides with high molecular weight, describes an excellent example of compositions with superior nasal absorption and increased maximum blood concentrations. According to this official gazette, this action effect can be positively achieved using a water-absorbing and basic gel-forming base such as hydroxypropylcellulose in combination with aggregate crystalline cellulose of particle diameter greater than 150 μm on the contrary to JP-6242888-B suggesting that a relatively small particle diameter of 20-150 μm is preferred as the preparation.
However, the present inventors have no information on the practical application of insulin formulations for nasal administration including these related prior arts. A composition that will enable nasal administration of insulin for practical use and particularly markedly increased nasal insulin absorption, is, therefore, still needed.